Abstract：
OBJECTIVE: To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm.
METHODS: Randomized, double-blind clinical trial follow-up plus cohort study.
METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
METHODS: Extremely or very preterm-born children aged 7 to 15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period.
METHODS: participation in an ongoing neuropediatric study (EpoKids), written informed consent.
METHODS: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited.
METHODS: term birth, informed consent.
METHODS: any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses.
METHODS: The electroretinogram (ERG) was performed with the RETeval device (LKC Technologies, Inc). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group.
METHODS: Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only).
RESULTS: No differences in ERG parameters between EPO (n = 52; 104 eyes) and placebo (n = 35; 70 eyes) subgroups were observed (all corrected P > .05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n = 52; 104 eyes) subgroup (coefficient/95% confidence interval = 0.53/0.21-0.85 and 0.36/0.13-0.60; P = .012 and .022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% confidence interval = -4.33/-6.88 to -1.78; P = .011). Secondary outcomes were comparable across subgroups.
CONCLUSIONS: Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.
METHODS: Randomized, double-blind clinical trial follow-up plus cohort study.
METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
METHODS: Extremely or very preterm-born children aged 7 to 15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period.
METHODS: participation in an ongoing neuropediatric study (EpoKids), written informed consent.
METHODS: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited.
METHODS: term birth, informed consent.
METHODS: any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses.
METHODS: The electroretinogram (ERG) was performed with the RETeval device (LKC Technologies, Inc). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group.
METHODS: Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only).
RESULTS: No differences in ERG parameters between EPO (n = 52; 104 eyes) and placebo (n = 35; 70 eyes) subgroups were observed (all corrected P > .05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n = 52; 104 eyes) subgroup (coefficient/95% confidence interval = 0.53/0.21-0.85 and 0.36/0.13-0.60; P = .012 and .022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% confidence interval = -4.33/-6.88 to -1.78; P = .011). Secondary outcomes were comparable across subgroups.
CONCLUSIONS: Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.
摘要：
目的：探讨围产期大剂量重组人促红细胞生成素(rhEPO)对极早产儿童视网膜和视功能的长期影响。
方法：随机化，双盲临床试验随访加队列研究。
方法：设置：眼科，苏黎世大学医院,苏黎世,瑞士。
方法：7-15岁的极度或非常早产儿童，先前在围产期随机接受高剂量rhEPO或安慰剂。
方法：参与正在进行的神经儿科研究（EpoKids），书面知情同意书（IC）。
方法：既往眼外伤或手术；与早产无关的视网膜或发育性疾病。招募了年龄相当的健康对照（HC）儿童。
方法：足月分娩，IC.
方法：任何眼/视觉异常，高屈光不正。干预状态（rhEPO/安慰剂）是未知的审查员和受试者在检查，只有在完成所有分析后，审查员才会脱盲。
方法：使用RETeval设备进行视网膜电图（ERG）（LKCTechnologies，Inc.,盖瑟斯堡医学博士）。眼科和正交检查排除了早产队列中的合并症和HC组的眼部疾病。
方法：Scotopic和明视ERG响应幅度和峰值时间（6个幅度；6个峰值时间）。次要结果是习惯性视力和颜色辨别表现（仅用于描述性摘要）。
结果：EPO（n=52;104眼）和安慰剂（n=35;70眼）亚组之间的ERG参数没有差异（所有校正p>0.05）。安慰剂组的两个视锥系统介导的峰值时间比HC（n=52；104眼）亚组稍慢（系数/95％置信区间（CI）=0.53/0.21至0.85和0.36/0.13至0.60；p=0.012和0.022）；EPO中主要是杆系统介导的峰值时间比HC亚组稍快（系数/95％CI=-4.33/-6.88-1.11；次要结局在亚组之间具有可比性。
结论：与安慰剂相比，对在围产期出生的极度或极早产的婴儿给予大剂量rhEPO对儿童视网膜功能没有可测量的影响。早产可能会导致小，可能对儿童视网膜功能的临床影响不明显，在围产期施用rhEPO可能会部分缓解。
方法：随机化，双盲临床试验随访加队列研究。
方法：设置：眼科，苏黎世大学医院,苏黎世,瑞士。
方法：7-15岁的极度或非常早产儿童，先前在围产期随机接受高剂量rhEPO或安慰剂。
方法：参与正在进行的神经儿科研究（EpoKids），书面知情同意书（IC）。
方法：既往眼外伤或手术；与早产无关的视网膜或发育性疾病。招募了年龄相当的健康对照（HC）儿童。
方法：足月分娩，IC.
方法：任何眼/视觉异常，高屈光不正。干预状态（rhEPO/安慰剂）是未知的审查员和受试者在检查，只有在完成所有分析后，审查员才会脱盲。
方法：使用RETeval设备进行视网膜电图（ERG）（LKCTechnologies，Inc.,盖瑟斯堡医学博士）。眼科和正交检查排除了早产队列中的合并症和HC组的眼部疾病。
方法：Scotopic和明视ERG响应幅度和峰值时间（6个幅度；6个峰值时间）。次要结果是习惯性视力和颜色辨别表现（仅用于描述性摘要）。
结果：EPO（n=52;104眼）和安慰剂（n=35;70眼）亚组之间的ERG参数没有差异（所有校正p>0.05）。安慰剂组的两个视锥系统介导的峰值时间比HC（n=52；104眼）亚组稍慢（系数/95％置信区间（CI）=0.53/0.21至0.85和0.36/0.13至0.60；p=0.012和0.022）；EPO中主要是杆系统介导的峰值时间比HC亚组稍快（系数/95％CI=-4.33/-6.88-1.11；次要结局在亚组之间具有可比性。
结论：与安慰剂相比，对在围产期出生的极度或极早产的婴儿给予大剂量rhEPO对儿童视网膜功能没有可测量的影响。早产可能会导致小，可能对儿童视网膜功能的临床影响不明显，在围产期施用rhEPO可能会部分缓解。
